Person: GÜRAN, TÜLAY
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GÜRAN
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TÜLAY
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Publication Metadata only The role of leptin, soluble leptin receptor, resistin, and insulin secretory dynamics in the pathogenesis of hypothalamic obesity in children(SPRINGER, 2009) BEREKET, ABDULLAH; Guran, Tulay; Turan, Serap; Bereket, Abdullah; Akcay, Teoman; Unluguzel, Goksenin; Bas, Firdevs; Gunoz, Hulya; Saka, Nurcin; Bundak, Ruveyde; Darendeliler, Feyza; Isguven, Pinar; Yildiz, Metin; Adal, Erdal; Sarikaya, Sevil; Baygin, Leyla Akin; Memioglu, Nihal; Onal, Hasan; Ercan, Oya; Haklar, GoncagulIn this study, we have investigated the role of leptin, soluble leptin receptor(sOb-R), resistin, and insulin secretory dynamics in the development of hypothalamic obesity. Children who had hypothalamo-pituitary tumor were divided into two groups. First group included obese-overweight (hypothalamic obese = HOB group, n = 23) and second group included non-obese children (hypothalamic non-obese = HNOB group, n = 16). Exogenously obese-overweight children (OB group, n = 22) were included as controls. Basal and second-hour serum glucose and insulin in oral glucose tolerance test (OGTT), basal serum leptin, sOb-R, resistin levels, and homeostasis model assessment (HOMA) indexes were compared between the groups. Age, sex, and pubertal status were similar in study groups. Median and interquartile ranges of body mass index (BMI) z scores were similar in HOB and OB groups (2.0 (1.5-2.1) and 2.1 (1.8-2.3), respectively). Serum leptin levels corrected for BMI were highest and total leptin/sOb-R ratios (free leptin index (FLI)) tended to be higher in HOB than HNOB and OB groups, indicating leptin resistance (leptin/BMI, 4.0 (1.6-5.2), 1.5 (0.8-3.1), and 2.5 (1.8-3.5); FLI, 2.0 (0.8-3.5), 0.6 (0.3-1.2), and 1.5 (1-2.3) in HOB, HNOB, and OB groups; respectively). Serum resistin levels were similar in groups (2.6 (1.9-3.1), 2.8 (1.7-3.4), and 3.0 (2.2-3.5) ng/ml in HOB, HNOB, and OB groups, respectively). Basal serum glucose, basal and second-hour insulin levels in OGTT, and HOMA index were higher in OB group than the HOB and HNOB groups, indicating insulin resistance in simple obesity; however, increment of insulin to same glycemic load in OGTT was highest in the HOB group indicating insulin dysregulation (p < 0.05). Hypothalamic obesity seems to be related to both dysregulated afferent (leptin) and efferent (insulin) neural outputs through the autonomic nervous system resulting in energy storage as fat.Publication Open Access Constitutional Growth Delay Pattern of Growth in Velo-Cardio-Facial Syndrome: Longitudinal follow up and final height of two cases(2008) BEREKET, ABDULLAH; Turan, Serap; Ozdemir, Nihal; Güran, Tülay; Akalın, Figen; Akçay, Teoman; Ayabakan, Canan; Yılmaz, Yüksel; Bereket, AbdullahWe report two patients with velo-cardio-facial syndrome (VCFS) who were admitted to our pediatric endocrinology clinic because of short stature and followed longitudinally until attainment of final height. Both patients followed a growth pattern consistent with constitutional delay of puberty with normal and near normal final height. Case 2 also had partial growth hormone (GH) deficiency and severe short stature (height SDS -3.4 SDS), but showed spontaneous catch-up and ended up with a final height of -2 SDS. These cases suggest that short stature in children with VCFS is due to a pattern of growth similar to that observed in constitutional delay of growth and puberty.Publication Metadata only Significance of acanthosis nigricans in childhood obesity(WILEY-BLACKWELL, 2008) BEREKET, ABDULLAH; Guran, Tulay; Turan, Serap; Akcay, Teoman; Bereket, AbdullahAim: Acanthosis nigricans (AN) is among the most common dermatologic manifestations of obesity and hyperinsulinism. In this study, we aimed to find the clinical and laboratory differences in obese children with AN and without AN (non-AN). Methods: In total, 160 obese children were included in the study. The duration of obesity, body mass index (BMI), BMI z-scores, birth weight, parental BMI, lipid profile, fasting and post-meal (PM) glucose and insulin levels were compared in 67 obese with AN and 93 obese without AN. Results: Age was similar in both groups. AN group had higher male to female ratio (42/25 in AN, 43/50 in non-AN; P = 0.03), higher BMI (30.3 +/- 6.1 in AN, 26.4 +/- 3.6 in non-AN; P < 0.001) and weight for height (162.6 +/- 28.8 in AN, 144.6 +/- 15.8 in non-AN; P < 0.001) than non-AN group. There were no significant differences between the groups in birth weight, parental BMI and blood pressure. AN group had higher fasting (19.9 +/- 16.2 mU/L in AN, 10.4 +/- 7.6 mU/L in non-AN; P < 0.001) and PM insulin (88.6 +/- 87.3 mU/L in AN, 51.1 +/- 42.0 mU/L in non-AN; P = 0.01) and homeostasis model assessment for insulin resistance (HOMA-IR) (4.0 +/- 2.5 in AN, 2.2 +/- 1.8 in non-AN; P < 0.001) than non-AN group. However, fasting and PM glucose, triglyceride, low-density lipoprotein-, high-density lipoprotein- and total cholesterol levels were similar in both groups. BMI was correlated with HOMA-IR in both groups (r = 0.40 for AN, r = 0.28 for non-AN). PM glucose and PM insulin were correlated in both groups (r = 0.56 for AN, r = 0.39 for non-AN). However, fasting glucose and fasting insulin were correlated in only non-AN (r = 0.25), but not in AN group. Conclusions: Obese children with AN show higher insulin levels and HOMA-IR. AN is an important predictor of the insulin resistance in childhood obesity. Insulin secretory dynamics seem to be disrupted in fasting state initially, which is reflected as the loss of fasting insulin-glucose correlation in AN group.Publication Metadata only Bone mineral density in children with non-cystic fibrosis bronchiectasis(KARGER, 2008) BEREKET, ABDULLAH; Guran, Tulay; Turan, Serap; Karadag, Bulent; Ersu, Refika; Karakoc, Fazilet; Bereket, Abdullah; Dagli, ElifBackground: Bronchiectasis presents as a common sequela of several chronic pulmonary diseases. Bone mineral density ( BMD) is generally decreased in children with cystic fibrosis ( CF). Although children with non-CF bronchiectasis have similar risk factors for osteopenia/osteoporosis, data on BMD in this group of patients are lacking. Objective: To evaluate BMD in children with non-CF bronchiectasis. Methods: In this study, we evaluated BMD of the radius and tibia in 32 children ( 17 girls) with non-CF bronchiectasis and in 23 healthy controls matched for age, sex and pubertal stage by quantitative ultrasound ( speed of sound). Daily calcium intake and pulmonary function tests and data about steroid use were noted. Results: Mean age was 12.5 +/- 4.6 years. Six children ( 18%) had moderate-to-severe lung disease (FEV1 < 60% predicted). All except 2 children ( 94%) were receiving inhaled steroids. There was no significant difference in BMD ( expressed as z- score) of the radius and tibia between the patient and control groups ( tibia z-scores: - 0.1+/-0.9 vs. - 0.8 +/- 0.8 and radius z- scores - 1.3 +/- 1.4 vs. - 1.0 +/- 0.9 in bronchiectasis patients and controls, respectively, p >0.05). However, more children with non-CF bronchiectasis had osteopenia ( z- scores between - 1 and - 2 SD) and osteoporosis ( z- score <= 2 SD) compared to the control group ( 62 vs. 30%, p = 0.019). There was a significant correlation between age and radius z- scores ( r = - 0.365, p = 0.04). There was no correlation between BMD and severity of lung illness, calcium intake or cumulative steroid doses. Conclusion: Osteopenia is more common in children with non-CF bronchiectasis compared to controls and the risk of osteoporosis and osteopenia increases with age. Copyright (C) 2007 S. Karger AG, Basel.Publication Open Access Hypogonadotropic Hypogonadism due to a Novel Missense Mutation in the First Extracellular Loop of the Neurokinin B Receptor(ENDOCRINE SOC, 2009-10-01) BEREKET, ABDULLAH; Guran, Tulay; Tolhurst, Gwen; Bereket, Abdullah; Rocha, Nuno; Porter, Keith; Turan, Serap; Gribble, Fiona M.; Kotan, L. Damla; Akcay, Teoman; Atay, Zeynep; Canan, Husniye; Serin, Ayse; O'Rahilly, Stephen; Reimann, Frank; Semple, Robert K.; Topaloglu, A. KemalContext: The neurokinin B (NKB) receptor, encoded by TACR3, is widely expressed within the central nervous system, including hypothalamic nuclei involved in regulating GnRH release. We have recently reported two mutations in transmembrane segments of the receptor and a missense mutation in NKB in patients with normosmic isolated hypogonadotropic hypogonadism (nIHH). Patients and Methods: Wesequenced the TACR3 gene in a family in which three siblings had nIHH. The novel mutant receptor thus identified was studied in a heterologous expression system using calcium flux as the functional readout. Results: All affected siblingswerehomozygousfor the His148Leu mutation, in the first extracellular loop of theNKBreceptor. The His148Leu mutant receptor exhibited profoundly impaired signaling in response to NKB (EC50 = 3 +/- 0.1 nM and > 5 mu M for wild-type and His148Leu, respectively). The location of the mutation in an extracellular part of the receptor led us also to test whether senktide, a syntheticNKBanalog, mayretain ability to stimulate the mutant receptor. However, the signaling activity of the His148Leu receptor in response to senktide was also severely impaired (EC50 = 1 +/- 1 nM for wild-type and no significant response of His148Leu to 10 mu M). Conclusions: Homozygosity for the TACR3 His148Leu mutation leads to failure of sexual maturation in humans, whereas signaling by the mutant receptor in vitro in response to either NKB or senktide is severely impaired. These observations further strengthen the link between NKB, the NKB receptor, and regulation of human reproductive function. (J Clin Endocrinol Metab 94: 3633 -3639, 2009)Publication Metadata only Increased QT dispersion in breath-holding spells(WILEY, 2004) AKALIN, FİGEN; Akalin, F; Turan, S; Guran, T; Ayabakan, C; Yilmaz, YAim: Breath-holding spells are common in infancy and early childhood, and patients are frequently referred to paediatric cardiology clinics for exclusion of heart disease. Recent data reveal subsequent development of epilepsy and neurocardiogenic syncope. Autonomic dysregulation and increased vagal stimulation leading to cardiac arrest and cerebral ischaemia is considered as the cause. Iron deficiency anaemia may be associated with these spells. We studied QT dispersion for the assessment of ventricular repolarization in these patients. Methods: The study group consisted of 19 girls and 24 boys between 3 and 108 mo of age (mean +/- SD = 22.7 +/- 17.7 mo); and the control group consisted of 13 girls and 12 boys between 3 and 57 mo of age (mean +/- SD = 22.9 +/- 15.1 mo). QT interval was measured; corrected QT interval (QTc), QT dispersion (QTd) and QTc dispersion (QTcd) were calculated from 12-lead surface electrocardiograms of the patients and the control group. Results: There was no statistically significant difference in terms of QT and QTc intervals between patient and control groups, while QTd and QTcd values were significantly increased in patients with breath-holding spells compared to the healthy children. QT dispersion was 59.5 +/- 35.9 ms and 44.8 +/- 11.9 ms, respectively, in patients and controls (p < 0.05). QTc dispersion was 102.1 +/- 41.9 ms and 79.6 +/- 24.6 ms, respectively (p < 0.01). The presence of iron deficiency did not effect the QT and QTc dispersion. Conclusion: QT dispersion is increased in patients with breath-holding spells, and this finding justifies further investigation for rhythm abnormalities and autonomic dysfunction in this patient group.Publication Metadata only Alopecia: association with resistance to thyroid hormones(2009) BEREKET, ABDULLAH; Guran, Tulay; Bircan, Rifat; Turan, Serap; Bereket, AbdullahResistance to thyroid hormone (RTH) syndrome is caused by thyroid hormone beta receptor (TRbeta) mutations. Goiter, learning disabilities, psychological abnormalities, sinus tachycardia, hearing deficits, short stature, and growth delay are among the most common symptoms in patients with RTH. Alopecia areata (AA) is an autoimmune disease of the hair follicle, frequently associated with other autoimmune disorders. In some cases local alopecia of different genetic backgrounds could be misdiagnosed as AA. We describe here clinical, biochemical and genetic features of a family having RTH syndrome, caused by a novel TRbeta mutation, coexistent with alopecia. Mutational analyses of the TRbeta gene and the hairless gene (HR) in genomic DNA were performed. The index patient is a 9-4/12 year-old boy with RTH due to a novel heterozygous missense mutation of the TRbeta gene (I353V), and diffuse, patchy alopecia without autoimmune thyroid disease. This mutation was also detected in his father and elder brother, who also have local alopecia. One of his paternal aunts and paternal grandmother have local alopecia and they have previously been operated for goiter. Although they refused any genetic analysis, the pre-operative medical report of the paternal aunt was compatible with RTH. A second paternal aunt has alopecia totalis universalis but has no RTH mutation in genomic DNA. Genomic DNA sequence of the HR gene of the family (index patient, two brothers, father, mother and second paternal aunt) was normal as well. CONCLUSION: We speculate that RTH due to a novel I353V TRbeta mutation could be causally related to different phenotypic expressions of alopecia in this family, either by a direct effect of unresponsiveness to T3 of the hair follicle or by the modulated action of the HR gene.